RESTORATION OF SPERMATOGENESIS BY ALLOGENEIC TRANSPLANTATION OF UNDIFFERENTIATED SERTOLI CELLS IN AN EXPERIMENTAL MODEL OF CRYPTORCHIDISM: LITERATURE REVIEW
DOI:
https://doi.org/10.52754/16948610_2026_2_7%20Keywords:
cryptorchidism, spermatogenesis, Sertoli cells, spermatogonial stem cells, cell therapyAbstract
Relevance. Cryptorchidism is one of the most common congenital anomalies of the male reproductive system and a major cause of impaired spermatogenesis and infertility. Despite advances in surgical and hormonal management, restoration of normal spermatogenic function remains incomplete in a substantial proportion of patients. Increasing evidence indicates that early disruption of germ cell development and dysfunction of Sertoli cells play a central role in the pathogenesis of cryptorchidism-associated infertility. In recent years, regenerative and cell-based therapeutic approaches, particularly involving Sertoli cells and spermatogonial stem cells, have emerged as promising strategies to reconstruct the spermatogenic niche. This review summarizes current knowledge on the physiology of spermatogenesis, the role of Sertoli cells, the pathophysiology of cryptorchidism, and the experimental and clinical progress of Sertoli cell–based and spermatogenic stem cell transplantation. Special emphasis is placed on translational challenges and future clinical applications.
References
Avarbock, M. R., et al. (2020). Cryopreservation of spermatogonial stem cells. Reproduction, 159(5), R201–R210. https://doi.org/10.1530/REP-19-0564
Brinster, R. L., & Zimmermann, J. W. (1994). Spermatogenesis following male germ-cell transplantation. Proceedings of the National Academy of Sciences, 91(24), 11298–11302. https://doi.org/10.1073/pnas.91.24.11298
Dufour, J. M., Hemendinger, R., Halberstadt, C. R., Gores, P., & Korbutt, G. S. (2010). Sertoli cells and immune privilege. Nature Reviews Immunology, 10(1), 8–19. https://doi.org/10.1038/nri2682
Fauser, B. C. J. M., et al. (2016). Autologous spermatogonial stem cell transplantation in patients with cancer. The Lancet, 387(10029), 2521–2523. https://doi.org/10.1016/S0140-6736(16)00310-4
França, L. R., & Russell, L. D. (1998). The testis of domestic animals. Journal of Andrology, 19(5), 536–550.
Gendrel, D., & Job, J. C. (1988). Endocrine abnormalities in cryptorchidism. Journal of Pediatrics, 113(2), 370–375.
Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., & Ferguson, T. A. (1995). Fas ligand–induced apoptosis as a mechanism of immune privilege. Science, 270(5239), 1189–1192. https://doi.org/10.1126/science.270.5239.1189
Griswold, M. D. (2016). Spermatogenesis: The commitment to meiosis. Physiological Reviews, 96(1), 1–17. https://doi.org/10.1152/physrev.00013.2015
Handel, M. A., & Schimenti, J. C. (2010). Genetics of mammalian meiosis. Annual Review of Genetics, 44, 105–133. https://doi.org/10.1146/annurev-genet-102209-163731
Hermann, B. P., et al. (2012). Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell, 11(5), 715–726. https://doi.org/10.1016/j.stem.2012.07.017
Huff, D. S., Fenig, D. M., Canning, D. A., Carr, M. G., & Zderic, S. A. (2001). Abnormal germ cell development in cryptorchidism. Hormone Research, 55(1), 11–17. https://doi.org/10.1159/000049973
Hutson, J. M., Balic, A., Nation, T., & Southwell, B. (2010). Cryptorchidism. Seminars in Pediatric Surgery, 19(3), 215–224. https://doi.org/10.1053/j.sempedsurg.2010.04.003
Kanatsu-Shinohara, M., et al. (2018). Biocompatible scaffolds for spermatogonial stem cell transplantation. Biomaterials, 156, 50–59. https://doi.org/10.1016/j.biomaterials.2017.11.019
Korbutt, G. S., Elliott, J. F., Ao, Z., Smith, D. K., Warnock, G. L., & Rajotte, R. V. (2000). Sertoli cells exert immunomodulatory effects on transplanted islets. Cell Transplantation, 9(4), 415–420. https://doi.org/10.1177/096368970000900401
Kubota, H., & Brinster, R. L. (2008). Spermatogonial stem cells. Biology of Reproduction, 79(3), 418–427.
Li, Z., et al. (2022). Artificial intelligence in the cultivation of spermatogonial stem cells. Frontiers in Cell and Developmental Biology, 10, 843921. https://doi.org/10.3389/fcell.2022.843921
Lukina, N. V. (2019). Environmental factors affecting spermatogenesis. Environmental Health Perspectives, 127(9), 96001. https://doi.org/10.1289/EHP3657
Malolina, E. A., & Kulibin, A. Y. (2012). Transplantation of Sertoli cells in the treatment of cryptorchidism. Experimental and Clinical Transplantation, 10(4), 309–316.
Mruk, D. D., & Cheng, C. Y. (2015). Sertoli–Sertoli and Sertoli–germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocrine Reviews, 36(1), 1–45. https://doi.org/10.1210/er.2014-1036
Nagano, M. C., et al. (2003). Transplantation of testis germ cells in mammals. Reproduction, 125(3), 277–286.
O’Donnell, L. (2020). Mechanisms of spermiogenesis and regulation of sperm maturation. Physiological Reviews, 100(3), 1225–1286. https://doi.org/10.1152/physrev.00051.2018
Ogawa, T., Dobrinski, I., & Brinster, R. L. (1999). Recipient preparation is critical for spermatogonial transplantation. Biology of Reproduction, 60(4), 963–969.
Rudenko, M. A. (2018). Molecular regulation of spermatogonial stem cells. Reproductive Biology, 18(4), 347–355.
Sato, T., et al. (2006). In vitro production of functional sperm. Nature, 441(7091), 321–324. https://doi.org/10.1038/nature04678
Schlatt, S., et al. (1999). Germ cell transplantation into the primate testis. Human Reproduction, 14(1), 144–150.
Shinohara, T. (2003). Spermatogonial stem cell self-renewal and development. Annual Review of Cell and Developmental Biology, 19, 547–570. https://doi.org/10.1146/annurev.cellbio.19.111301.112106
Smith, L. B., & Walker, W. H. (2014). The regulation of spermatogenesis by Sertoli cells. Annual Review of Physiology, 76, 271–297. https://doi.org/10.1146/annurev-physiol-021113-170314
Sofikitis, N., et al. (1999). Germ cell transplantation and spermatogenesis. Human Reproduction Update, 5(4), 366–377.
Wu, Y., et al. (2015). CRISPR/Cas9-mediated genome editing in human spermatogonial stem cells. Cell Stem Cell, 17(4), 450–460. https://doi.org/10.1016/j.stem.2015.09.007
Zakharova, E. V. (2017). Genetic regulation of meiosis in spermatogenesis. Russian Journal of Genetics, 53(6), 643–652.
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Copyright (c) 2026 Эмир Жамынчиев , Роман Калматов , Иметкул Исмаилов , Жоомарт Зубаиров , Эртегин Байгашкаев , Тимур Пайзилдаев , Искендербек Абдирайимов
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